Explore the vast range of titles available.

Background Progression-free survival (PFS) is a surrogate endpoint widely used for overall survival (OS) in oncology. Validation of PFS as a surrogate must be done for each indication and each intervention. We aimed to identify all studies evaluating the validity of PFS as a surrogate for OS in oncology, and to describe their methodological characteristics. Methods We conducted a systematic review by searching MEDLINE via PubMed and the Cochrane Library with no limitation on time, selected relevant studies and extracted data in duplicate on how surrogacy was evaluated (meta-analytic approach, assessment of correlation and level of evaluation). Results We identified 91 studies evaluating the validity of PFS as a surrogate for OS in 24 cancer localisations. Although a meta-analytic approach was used in 83 (91%) studies, the methods used to validate PFS as a surrogate of OS were heterogeneous across studies. Of the 47 studies concluding that PFS is a good surrogate for OS, for 15 (32%), there was no quantitative argument for surrogacy. Conclusions Although most studies used a meta-analytic approach as recommended, our methodological review highlights heterogeneity in methods and reporting, which stresses the importance of developing and applying clear recommendations in this area.

PurposeTo assess the effect of venovenous extracorporeal membrane oxygenation (ECMO) compared to conventional management in patients with severe acute respiratory distress syndrome (ARDS).MethodsWe conducted a systematic review and individual patient data meta-analysis of randomised controlled trials (RCTs) performed after Jan 1, 2000 comparing ECMO to conventional management in patients with severe ARDS. The primary outcome was 90-day mortality. Primary analysis was by intent-to-treat.ResultsWe identified two RCTs (CESAR and EOLIA) and combined data from 429 patients. On day 90, 77 of the 214 (36%) ECMO-group and 103 of the 215 (48%) control group patients had died (relative risk (RR), 0.75, 95% confidence interval (CI) 0.6–0.94; P = 0.013; I2 = 0%). In the per-protocol and as-treated analyses the RRs were 0.75 (95% CI 0.6–0.94) and 0.86 (95% CI 0.68–1.09), respectively. Rescue ECMO was used for 36 (17%) of the 215 control patients (35 in EOLIA and 1 in CESAR). The RR of 90-day treatment failure, defined as death for the ECMO-group and death or crossover to ECMO for the control group was 0.65 (95% CI 0.52–0.8; I2 = 0%). Patients randomised to ECMO had more days alive out of the ICU and without respiratory, cardiovascular, renal and neurological failure. The only significant treatment-covariate interaction in subgroups was lower mortality with ECMO in patients with two or less organs failing at randomization.ConclusionsIn this meta-analysis of individual patient data in severe ARDS, 90-day mortality was significantly lowered by ECMO compared with conventional management.

Population-adjusted indirect comparisons (PAICs) were developed in the 2010s to allow for comparisons between two treatments evaluated in different trials while accounting for differences in patient characteristics if individual patient data (IPD) are available for only one trial. Such comparisons are increasingly used in market access applications when a pharmaceutical company compares its new treatment (with IPD available) to another treatment developed by a competitor (with only aggregated data available). This study aimed to describe the characteristics of these PAICs, assess their methodology, and describe the reported results. Original articles reporting the use of at least one PAIC were searched on PubMed between January 1, 2010 and April 2, 2022. Two reviewers independently selected articles and extracted data. We included 133 publications reporting the results of 288 PAICs. Half of the articles were published on or after May 7, 2020, and 71 (53%) pertained to onco-hematology. The pharmaceutical industry was involved in 130 (98%) articles. Key methodological aspects were reported inconsistently, with only three articles adequately reporting all aspects. A total of 161 (56%) articles reported a statistically significant benefit for the treatment evaluated on IPD. Conversely, only one PAIC significantly favored the treatment evaluated on aggregated data. Although the number of published PAICs is increasing, the methodology and transparency need to be improved. Moreover, our study strongly suggests a reporting bias. This situation calls for strengthening guidelines to improve trust in PAIC results and thus their reliability in market access applications. [Display omitted] •Population-adjusted indirect comparisons have increased in popularity recently.•Most publications focused on oncologic and hematologic pathologies.•Methodology and reporting standards were insufficient.•Collected results suggest a major reporting and publication bias.•We propose some reporting guidelines to strengthen confidence in these methods.

The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration-approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001). The main study limitation was that we considered only the publication describing the results for the primary outcomes. Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article.

The timing of renal replacement therapy (RRT) for severe acute kidney injury is highly debated when no life-threatening complications are present. We assessed whether a strategy of delayed versus early RRT initiation affects 28-day survival in critically ill adults with severe acute kidney injury. In this systematic review and individual patient data meta-analysis, we searched MEDLINE (via PubMed), Embase, and the Cochrane Central Register of Controlled Trials for randomised trials published from April 1, 2008, to Dec 20, 2019, that compared delayed and early RRT initiation strategies in patients with severe acute kidney injury. Trials were eligible for inclusion if they included critically ill patients aged 18 years or older with acute kidney injury (defined as a Kidney Disease: Improving Global Outcomes [KDIGO] acute kidney injury stage 2 or 3, or, where KDIGO was unavailable, a renal Sequential Organ Failure Assessment score of 3 or higher). We contacted the principal investigator of each eligible trial to request individual patient data. From the included trials, any patients without acute kidney injury or who were not randomly allocated were not included in the individual patient data meta-analysis. The primary outcome was all-cause mortality at day 28 after randomisation. This study is registered with PROSPERO (CRD42019125025). Among the 1031 studies identified, one study that met the eligibility criteria was excluded because the recruitment period was not recent enough, and ten (including 2143 patients) were included in the analysis. Individual patient data were available for nine studies (2083 patients), from which 1879 patients had severe acute kidney injury and were randomly allocated: 946 (50%) to the delayed RRT group and 933 (50%) to the early RRT group. 390 (42%) of 929 patients allocated to the delayed RRT group and who had available data did not receive RRT. The proportion of patients who died by day 28 did not significantly differ between the delayed RRT group (366 [44%] of 837) and the early RRT group (355 [43%] of 827; risk ratio 1·01 [95% CI 0·91 to 1·13], p=0·80), corresponding to an overall risk difference of 0·01 (95% CI −0·04 to 0·06). There was no heterogeneity across studies (I2=0%; τ2=0), and most studies had a low risk of bias. The timing of RRT initiation does not affect survival in critically ill patients with severe acute kidney injury in the absence of urgent indications for RRT. Delaying RRT initiation, with close patient monitoring, might lead to a reduced use of RRT, thereby saving health resources. None.

ObjectiveTo evaluate the consistency of causal statements in observational studies published in The BMJ.DesignReview of observational studies published in a general medical journal.Data sourceCohort and other longitudinal studies describing an exposure-outcome relationship published in The BMJ in 2018. We also had access to the submitted papers and reviewer reports.Main outcome measuresProportion of published research papers with ‘inconsistent’ use of causal language. Papers where language was consistently causal or non-causal were classified as ‘consistently causal’ or ‘consistently not causal’, respectively. For the ‘inconsistent’ papers, we then compared the published and submitted version.ResultsOf 151 published research papers, 60 described eligible studies. Of these 60, we classified the causal language used as ‘consistently causal’ (48%), ‘inconsistent’ (20%) and ‘consistently not causal’(32%). Eleven out of 12 (92%) of the ‘inconsistent’ papers were already inconsistent on submission. The inconsistencies found in both submitted and published versions were mainly due to mismatches between objectives and conclusions. One section might be carefully phrased in terms of association while the other presented causal language. When identifying only an association, some authors jumped to recommending acting on the findings as if motivated by the evidence presented.ConclusionFurther guidance is necessary for authors on what constitutes a causal statement and how to justify or discuss assumptions involved. Based on screening these papers, we provide a list of expressions beyond the obvious ‘cause’ word which may inspire a useful more comprehensive compendium on causal language.

Background There is an increasing number of meta-analyses including data from non-randomized studies for therapeutic evaluation. We aimed to systematically assess the methods used in meta-analyses including non-randomized studies evaluating therapeutic interventions. Methods For this methodological review, we searched MEDLINE via PubMed, from January 1, 2013 to December 31, 2013 for meta-analyses including at least one non-randomized study evaluating therapeutic interventions. Etiological assessments and meta-analyses with no comparison group were excluded. Two reviewers independently assessed the general characteristics and key methodological components of the systematic review process and meta-analysis methods. Results One hundred eighty eight meta-analyses were selected: 119 included both randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSI) and 69 only NRSI. Half of the meta-analyses ( n  = 92, 49 %) evaluated non-pharmacological interventions. “Grey literature” was searched for 72 meta-analyses (38 %). An assessment of methodological quality or risk of bias was reported in 135 meta-analyses (72 %) but this assessment considered the risk of confounding bias in only 33 meta-analyses (18 %). In 130 meta-analyses (69 %), the design of each NRSI was not clearly specified. In 131 (70 %), whether crude or adjusted estimates of treatment effect for NRSI were combined was unclear or not reported. Heterogeneity across studies was assessed in 182 meta-analyses (97 %) and further explored in 157 (84 %). Reporting bias was assessed in 127 (68 %). Conclusions Some key methodological components of the systematic review process—search for grey literature, description of the type of NRSI included, assessment of risk of confounding bias and reporting of whether crude or adjusted estimates were combined—are not adequately carried out or reported in meta-analyses including NRSI.

BackgroundEpidemiology of spontaneous pneumothorax has been scantily studied. We aimed to assess the incidence of spontaneous pneumothorax and describe patients’ characteristics with respect to age, sex, seasonal occurrence, primary or secondary character, surgical management and rehospitalisations on a large-scale database.MethodsData from all patients aged ≥14 years and hospitalised with a diagnosis of non-traumatic pneumothorax in France from 2008 to 2011 were retrieved from the National Hospitalisation Database.ResultsThere were 59 637 hospital stays corresponding to 42 595 patients. Twenty-eight per cent of patients were rehospitalised at least once during the 4-year period. Annual rate of pneumothorax could be estimated at 22.7 (95% CI 22.4 to 23.0) cases for 100 000 habitants. The women to men ratio was 1:3.3. Mean age was significantly higher in women than in men (41±19 vs 37±19 years, p<0.0001). No seasonal variation was observed. A surgical procedure was performed in 14 352 hospital stays (24%). In the group of patients aged <30 years, there was no statistical difference between men and women with regard to type of pneumothorax (primary or secondary), type of hospitalisation unit (surgery vs medicine), treatment modality (surgery or not), intensive care unit (ICU) admission and hospital stay duration. Rehospitalisation was more frequent in women than in men (56% vs 52%, p<0.0001). In the 30–49 years age group, surgery and rehospitalisation were more frequent in women than in men (each, p<0.001). In the 50–64 years age group, surgical procedures and rehospitalisations were more frequent in men than in women (p=0.002 and p<0.0001, respectively).ConclusionsSex and age are determinant factors in the course of spontaneous pneumothorax.

To describe patient and public involvement (PPI) in randomized controlled trials (RCTs) addressing a chronic condition and to analyze whether PPI is associated with trial characteristics. We used PubMed search to identify RCTs addressing a chronic condition and published in journals with a mandatory PPI statement. Across 101 RCTs; 40 (40%) reported PPI at any stage of the research process. PPI contribution occurred mostly at the design stage of RCTs (n = 36), especially for assessing the burden of the intervention (n = 24), and at the conduct stage (n = 21), with the elaboration of communication materials (n = 14). Less than one-third (13/40) of RCTs included PPI in the development or choice of outcome measures. As compared with non-PPI RCTs, PPI RCTs more frequently were published in The BMJ, had a corresponding author from the United Kingdom, reported a public funding source, had a higher inclusion rate, used usual care as a control and evaluated a digital intervention. PPI RCTs were associated with less frequent use of placebo as a control group. Our results underline that PPI is not uncommon in RCTs of chronic conditions but infrequently occurred at a key stage. Yet, the engagement of patients as a real partner in RCTs of chronic conditions should be enhanced.

Background Suboptimal prescribing, including the prescription of potentially inappropriate medications (PIM), is frequent in patients aged 65 years and older. PIMs are associated with adverse drug events, which may lead to hospital admissions and readmissions for the most serious cases. Several tools, known as lists of PIMs, can detect suboptimal prescription. Objective This systematic review aimed to identify which lists of PIMs are associated with hospital readmission of older patients. Patients and Methods MEDLINE, the Cochrane Library, EMBASE, and clinicaltrials.gov were searched for the period from 1 January 1991 up to 12 May 2022 to identify original studies assessing the association between PIMs and hospital readmissions or emergency department (ED) revisits within 30 days of discharge in older patients. This study is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Checklist, and the risk of bias was assessed with the Newcastle–Ottawa Quality Assessment Scale for Cohort Studies (NOS) and the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Results A total of six studies presenting four different lists of PIMs were included. Readmission rates varied from 4.3 to 25.5% and the odds ratio (OR) between PIMs and hospital readmission varied from 0.92 [95% confidence interval (CI) 0.59; 1.42] to 6.48 [95% CI 3.00; 14.00]. Only two studies found a statistically significant association between a list of PIMs and hospital readmission. These two studies used different tools: the Screening Tool of Older Person’s Prescriptions (STOPP) and the Screening Tool to Alert Doctors to Right Treatment (START) and a combination of Beers Criteria® and STOPP and START. Conclusion This systematic review shows that the association between list of PIMs and 30-day unplanned readmissions remains unclear and seems dependent on the PIM detection tool. Further studies are needed to clarify this association. PROSPERO registration number CRD42021252107.